Journal of Natural Products 2006-07-01

Chamazulene carboxylic acid and matricin: a natural profen and its natural prodrug, identified through similarity to synthetic drug substances.

Mai Ramadan, Susanne Goeters, Bernhard Watzer, Eva Krause, Klaus Lohmann, Rudolf Bauer, Bernd Hempel, Peter Imming

文献索引：J. Nat. Prod. 69 , 1041-5, (2006)

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摘要

Chamazulene carboxylic acid (1) is a natural profen with anti-inflammatory activity and a degradation product of proazulenic sesquiterpene lactones, e.g., matricin. Both 1 and proazulenes occur in chamomile (Matricaria recutita), yarrow (Achillea millefolium), and a few other Asteraceae species. It was isolated in improved yields, characterized physicochemically, and found to be an inhibitor of cyclooxygenase-2, but not of cyclooxygenase-1. It had anti-inflammatory activity in several animal models with local and systemic application. When human volunteers were given matricin orally, plasma levels of 1 were found to be in the micromolar range. Matricin was converted to 1 in artificial gastric fluid, but not in artificial intestinal fluid. Matricin and the yarrow proazulenes are proposed to be anti-inflammatory through conversion to 1. Intriguingly, the biological activity of the natural compound 1 was found because of its similarity to fully synthetic drug substances. This is the reverse process of the common lead function of natural compounds in drug discovery.